WO2018153956A1 - Médicament destiné au traitement de malignité - Google Patents

Médicament destiné au traitement de malignité Download PDF

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Publication number
WO2018153956A1
WO2018153956A1 PCT/EP2018/054339 EP2018054339W WO2018153956A1 WO 2018153956 A1 WO2018153956 A1 WO 2018153956A1 EP 2018054339 W EP2018054339 W EP 2018054339W WO 2018153956 A1 WO2018153956 A1 WO 2018153956A1
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WO
WIPO (PCT)
Prior art keywords
receptor
hla
type
antibodies
expression pattern
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PCT/EP2018/054339
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German (de)
English (en)
Inventor
Wolfgang Würfel
Original Assignee
Wuerfel Wolfgang
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Wuerfel Wolfgang filed Critical Wuerfel Wolfgang
Priority to EP18707335.8A priority Critical patent/EP3586132B1/fr
Priority to CA3054495A priority patent/CA3054495A1/fr
Priority to US16/488,523 priority patent/US20190376968A1/en
Priority to SG11201907869VA priority patent/SG11201907869VA/en
Priority to ES18707335T priority patent/ES2951762T3/es
Priority to JP2019567781A priority patent/JP2020510695A/ja
Publication of WO2018153956A1 publication Critical patent/WO2018153956A1/fr
Priority to IL26889719A priority patent/IL268897A/en
Priority to JP2022189482A priority patent/JP2023027134A/ja

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56966—Animal cells
    • G01N33/56977—HLA or MHC typing
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand

Definitions

  • the present invention relates to the field of providing medicaments for the treatment of malignancies.
  • HLA human leucocyte antigen
  • HLA groups A. B and C (MHC-I), which are essentially all adult and
  • HLA groups D (DR, DP, DQ, etc., MHC-II), which play an important role in
  • HLA groups E, F and G which identify embryonic cells, especially at the so-called invasion front;
  • HLA groups H and following, the so-called pseudo-genes.
  • Malignant cells can express typical embryonic HLA groups (ie HLA-E, HLA-F and / or HLA-G) on their surface.
  • Embryonic HLA groups can help to prevent malignant cells from attacking the nonspecific and / or specific immune system of their own organism.
  • HLA groups on the surface of the cells enable them to activate corresponding receptors on immunocompetent cells.
  • they are receptors that, upon activation, inhibit the function of these immunocompetent cells, such as the killer immunoglobulin-like receptors (KIR) on the natural killer cells or the leukocyte immunoglobulin-like receptors (LILR) on the lymphocytes.
  • KIR killer immunoglobulin-like receptors
  • LILR leukocyte immunoglobulin-like receptors
  • the antigens HLA-E, -F and -G on the embryonic prevent
  • Pregnancy dar. A rejection reaction is omitted and the genetically semi-foreign (paternal third party 50%), or foreign (in egg or embryo donations or surrogacy 100%) embryo can be discharged.
  • Malignant tumors of various tissues are able to make use of this embryonic escape mechanism, thus preventing or reducing the immune defense. As a result, they are also able to counteract some therapeutic strategies, ie to inhibit the strategy based on an attack. For this reason, it may be beneficial to involve the immune system to treat the malignancy.
  • EP 2 561 890 A1 discloses production processes for antitumor medicaments in which, after determining an expression pattern of a malignant cell, embryonic HLA groups expressed there are masked or destroyed.
  • the masked or destroyed HLA groups can no longer inhibit the immune system, so that is expected to attack the immunocompetent cells. For this purpose, a masking of all possible malignant cells is necessary.
  • masking of the HLA groups may also be
  • a method according to the invention for the provision of a medicament for the treatment of a malignancy involving the respectively individually associated immune system comprises determining the individual communication structure between the malignancy and the immune system and the provision of antibodies.
  • At least one expression pattern of embryonic HLA groups located on the malignant tumor is determined, as well as at least one on / in
  • immunocompetent cells of the immune system present receptor status or type. Even histopathologically identically classified tumors or metastases may have different patterns of expression from one localization to another localization, either individually or intraindividually. Therapies, e.g. Administration of chemotherapeutic agents or hormone antagonists may further influence expression patterns.
  • Determining at least one receptor status, in particular receptor type refers to at least one receptor type that is capable of at least a part of the receptor
  • Receptor types of the respective receptor status are a class of surface or transmembrane proteins that are expressed by the immunocompetent cells on their surface and initiate signaling pathways by signal transduction. Inhibitory action is intended here to denote the immunomodulatory effect which reduces or prevents the cytotoxic activity of immunocompetent cells. This signaling pathway can be triggered, for example, via the immunoreceptor tyrosine-based inhibitory motif (ITIM), ie cytoplasmic phosphorylation.
  • ITIM immunoreceptor tyrosine-based inhibitory motif
  • antibodies refers to antibodies of the type which specifically bind as ligands to the at least one particular type of receptor, but which do not inhibit the associated immunocompetent cell and otherwise block or mask the receptor such that the at least part of the expression pattern does not exist there or can bind only with less effect.
  • the antibodies provided by the invention are capable of exerting no inhibitory effect on the immunocompetent cells by binding to the receptor, i. have no intrinsic activity.
  • the expression patterns of embryonic HLA groups of the malignant cell upon binding to the receptor exert an inhibitory effect on the immunocompetent cells.
  • determining the expression pattern comprises a
  • the determination of the expression pattern further comprises the quantitative determination of a
  • expression patterns or expression levels can be determined by known methods, such as RNA sequencing, DNA microarrays, quantitative PCR
  • malignant cell also includes metastatic cells of the primary malignancy.
  • the method according to the invention is carried out individually for preferably several, particularly preferably for all metastases, in order to check for any individual differences of the
  • the at least one type of receptor is typically expressed as a transmembrane protein on the surface of the immunocompetent cells.
  • the at least one type of receptor comprises one or more of the following: KIR receptors (killer immunoglobulin-like receptors), NKG2 receptors, LIL-R receptors
  • NKG2 receptors can bind HLA-E.
  • some LIL receptors in particular LIL Bl, LIL B2 and LIL B4, can bind HLA-F.
  • KIR 2DL3 or LIL A2 can bind HLA-G.
  • the antibodies provided are of the type to bind to at least one receptor type.
  • the antibodies designated as anti-IR 2DS1 bind as ligands to receptors of the KIR 2DS1 type.
  • Anti-KIR 2DS4 antibodies can bind to KIR 2DS4 receptors.
  • determining the receptor type may also take into account which receptors are applied to the individual.
  • the checking of which receptors are applied to the individual can be carried out, for example, by means of gene or expression analysis. If a particular type of receptor is not present in the individual, administration of antibodies to this type of receptor is not indicated.
  • the immunocompetent cells include NK cells
  • the method further comprises providing activating antibodies of the type that bind to the receptor after binding to a receptor
  • the method may further comprise determining whether HLA-C is overexpressed. In overexpression of HLA-C can its
  • Expression pattern and a second receptor type can be determined for this expression pattern; namely, one which is capable of binding at least part of the HLA-C expression pattern as a ligand and, based on this binding, one exert activating effect on immunocompetent cells.
  • the second receptor type may be a receptor type from the group of KIR-DS receptors which may exert an activating effect on NK cells.
  • activating receptors that bind to HLA-C are KIR 2DS1, KIR 2DS2 or KIR 2DS4.
  • KIR-DS receptors can activate immunocompetent cells to produce, for example, growth-promoting and tumor-promoting substances such as cytokines or growth factors.
  • the second type of receptor may be capable of binding at least a portion of the HLA-C expression pattern as a ligand and, based on this binding
  • the second receptor type may be a receptor type from the group of KIR-DL receptors which may exert an inhibitory effect on NK cells.
  • inhibitory receptors that bind to HLA-C are KIR 2DL1, KIR 2DL2, KIR 2DL3 or KIR 3DL3.
  • second antibodies of the type can be provided that specifically bind to the second receptor type but do not inhibit or activate the associated immunocompetent cell, simultaneously blocking or masking the second receptor such that the at least one portion of the HLA-C -Expressionsmusters there or can bind only with less effect.
  • the invention provides antibodies, which by a
  • the use of the invention comprises blocking or masking receptors of the at least one particular receptor type on immunocompetent cells by means of the antibodies.
  • the antibodies In such use of the antibodies, the binding of malignant cell-expressed embryonic HLA groups to the receptors of the at least one particular receptor type on the immunocompetent cells is prevented or reduced.
  • the antibodies Preferably, have a high affinity for the receptor type, in particular comparable to, greater than or substantially greater than the affinity of the embryonic HLA groups of the malignant cells.
  • the affinity is high enough to prevent diffusion and / or competitive displacement of the antibodies.
  • the use of the antibodies may be local or systemic.
  • Local use includes, for example, injection into or near the malignancy.
  • systemic use includes administration in one of the following ways: oral, nasal, sublingual, rectal, subcutaneous, intravenous, percutaneous, etc.
  • blocking or masking may occur in vitro with subsequent transfusion of the immunocompetent cells, for example, to avoid systemic side effects.
  • Immunocompetent cells are removed, exposed to the antibodies and backfused after masking.
  • the cell whose expression pattern has been determined and / or the immunocompetent cells whose receptors are specifically bound by the antibodies come from one and the same patient, for example in order to avoid systemic side effects.
  • Embodiments may be particularly preferred if the inter-individual variation in the expression of embryonic HLA groups is large.
  • the immunocompetent cells whose receptors are specifically bound by the antibodies can be from a donor.
  • the donor may be a third party who is not suffering from the malignancy.
  • the immunocompetent cells may be injected following blockade or masking of the receptors and used to treat the malignancy whose expression has been determined by embryonic HLA groups.
  • FIG. 1 is a flowchart of a method according to an exemplary embodiment
  • FIG. 2 shows a schematic representation of three malignant cells of different individuals on which a method according to an exemplary embodiment can be carried out
  • FIG. Figure 3 is a schematic representation of a malignant cell and an immunocompetent cell, with binding between an embryonic HLA group and a receptor of the immunocompetent cell,
  • FIG. 4 shows a schematic representation of a malignant cell and an immunocompetent cell on which a method according to an exemplary embodiment can be carried out
  • FIG. 5 shows a schematic representation of a malignant cell and an immunocompetent cell on which a method according to an exemplary embodiment can be carried out
  • FIG. 6 shows a schematic representation of a malignant cell and two immunocompetent cells on which a method according to an exemplary embodiment can be carried out
  • FIG. Figure 7 is a schematic representation of a malignant cell and immunocompetent cell, with a receptor of the immunocompetent cell masked by an antibody according to one embodiment.
  • FIG. 1 shows a flowchart of a method 10 for providing a medicament.
  • the method 10 includes determining 12 an expression pattern, determining 14 at least one receptor type, and providing 16 antibodies.
  • determining expression pattern 12 expressions of embryonic HLA groups located on the malignant are determined.
  • a type of receptor capable of expressing at least a portion of the expression pattern of the embryonic HLA groups is determined bind as a ligand and exert an inhibitory effect on the immune-competent cells based on this binding.
  • the antibodies provided in step 16 are of the type that specifically bind as ligands to the at least one particular type of receptor of the immunocompetent cells and block or mask the receptor such that the at least one part of the immunosupportive cell
  • FIG. 2 shows a schematic representation of three malignant cells 20a, 20b, 20c of different individuals A, B and C, on which a method according to the invention can be carried out.
  • a method according to the invention can be carried out.
  • Malignoma cells 20a, 20b, 20c a respective expression pattern can be determined, in particular an individual for the respective individual or the respective malignancy individual expression pattern.
  • the three malignant cells 20a, 20b, 20c differ in their individual communication structure with the immune system.
  • a first malignant cell 20a has been taken from the individual A.
  • Malignant cell 20a may have been taken as part of a tissue sample of a malignancy of subject A.
  • the malignant cell 20a has on its surface a plurality of membrane proteins (not shown). Some of these membrane proteins belong to the embryonic HLA groups.
  • the malignant cell 20a has, in particular, embryonic HLA groups 24a of the HLA-E type and of the HLA-G type (but not of the HLA-F type). An expression pattern 26a of the embryonic HLA groups 24a expressed by the malignant cell 20a can thus be determined.
  • a second malignant cell 20b taken from an individual B may differ, partially differ or completely differ in the embryonic HLA groups 24b it expresses from those expressed by the first malignant cell 20a.
  • the second malignant cell 20b expresses HLA-F embryonic HLA groups 24b.
  • the expression pattern 26c comprises the embryonic HLA groups 24c of the type HLA-F and of the HLA-G type.
  • At least one receptor type is determined which is capable of binding one of the embryonic HLA groups contained in the expression pattern as a ligand and, based on this binding, exerting an inhibitory effect on immunocompetent cells.
  • a cellular dialogue takes place, and this interaction may be, for example have an activating or inhibitory effect.
  • the identification of cells is also based on such receptor-ligand binding.
  • FIG. 3 shows a schematic representation of a malignant cell 20 and a
  • immunocompetent cell is characteristic of an individual communication structure between the malignant and the immune system. This inhibitory effect has to
  • Consequence that an immune response of the immunocompetent cell 30 is substantially omitted.
  • FIG. 4 shows a schematic representation of a malignant cell 20 and a
  • immunocompetent cell 30 on which a method according to the invention can be carried out.
  • this embodiment illustrates how at least one receptor type can be determined based on a specific expression pattern. This provision contributes to the individual communication structure between the
  • an expression pattern 26 of embryonic HLA groups comprising HLA groups of the type HLA-F can be determined on the malignant cell 20.
  • Immunocompetent cell 30 is a lymphocyte.
  • One receptor type 32 that meets the above requirements is LILR Bl (leucocyte immunoglobulin-like receptor B 1).
  • the malignant cell 20 could bind to the inhibitory receptor 32 of the lymphocyte 30 by means of the HLA group 24 and thus cause an inhibition of the immune system. This represents an escape mechanism of the malignant cell to escape the attack of the immune system.
  • Expression pattern 26 and the particular type of receptor 32 provided an antibody that prevents this escape mechanism.
  • the provision of the antibodies can be carried out, for example, according to known preparation or isolation methods, such as the hybridoma technique.
  • FIG. Figure 5 shows a schematic representation of another malignant cell 20 and a lymphocyte 30 on which a method of providing a medicament can be performed.
  • an expression pattern 26 of embryonic HLA groups expressed by the malignant cell can be determined at the malignant cell 20.
  • Expression pattern 26 comprises HLA groups 24 of the type HLA-E and HLA-G.
  • this embodiment illustrates how, based on a particular expression pattern, several types of receptors can be determined that are specific to the individual
  • two receptor types 32 are determined, namely NKG2 and KIR receptors. These two receptor types 32 are capable of one of the expressing HLA embryonic groups 24 as a ligand, and having an inhibitory effect on the HLA-group based on the binding of the embryonic HLA group
  • the NKG2 receptors are able to bind HLA groups of the type HLA-E as a ligand and to exert an inhibitory effect on the lymphocyte based on the binding of the HLA-E group.
  • the KIR receptors are capable of ligating HLA-type HLA groups and exerting an inhibitory effect on the lymphocyte based on the binding of the HLA-G group. If, as in the illustrated example, multiple receptor types are determined, then these multiple receptor types, or at least a portion thereof, may be blocked or masked, with some hierarchy of blockage being taken into account.
  • the type KIR 2DL4 receptor is considered to be particularly important for the inhibitory effect. To avoid side effects can therefore be a restriction to the most important
  • Receptor types may be preferred, in particular with a masking in vivo to avoid systemic side effects.
  • individual receptor types may be blocked step by step, e.g. if a relative classification of the inhibitory effects of several types of receptor in individual cases is not yet known. In the absence or inadequate immune response, one or more further or other steps can be taken in further steps
  • Receptor types are blocked. Such an approach may be particularly preferred for in vivo masking to avoid systemic side effects. Thus, a finely dosed control of the masking and the response of the immune system can be made.
  • FIG. Figure 6 shows a schematic representation of a malignant cell 20 and two immunocompetent cells, namely a lymphocyte 30a and an NK cell 30b, to which a method of providing a medicament can be performed.
  • an expression pattern 26 of embryonic HLA groups expressed by the malignant cell can be determined at the malignant cell 20.
  • the expression pattern 26 comprises HLA groups 24 of the type HLA-F and HLA-G.
  • this embodiment illustrates that the particular receptor types may have an inhibitory effect on various immunocompetent cells, such as lymphocytes and NK cells. It is thus the individual communication structure between malignancy and the
  • LIL-R leucocyte immunoglobulin-like receptor
  • KIR killer cell immunoglobulin-like receptor
  • the LIL receptors are capable of binding HLA-type HLA-F ligands and exerting an inhibitory effect on the lymphocyte 30a based on the binding of the HLA-F group.
  • the KIR receptors are able to bind HLA groups of the HLA-G type as a ligand and to exert an inhibitory effect on the NK cells 30b based on the binding of the HLA-G group.
  • the two receptor types 32 are capable of ligating one of the embryonic HLA embryonic groups 24 as ligands and exerting an inhibitory effect on various immunocompetent cells 30a, 30b based on the binding of the embryonic HLA group.
  • FIG. 7 shows a schematic representation of a malignant cell 20 with an HLA group 24 and an immunocompetent cell 30 with a receptor 32. Furthermore, FIG. 7 shows a schematic representation of a malignant cell 20 with an HLA group 24 and an immunocompetent cell 30 with a receptor 32. Furthermore, FIG. 7 shows a schematic representation of a malignant cell 20 with an HLA group 24 and an immunocompetent cell 30 with a receptor 32. Furthermore, FIG. FIG. 7 shows a schematic representation of a malignant cell 20 with an HLA group 24 and an immunocompetent cell 30 with a receptor 32. Furthermore, FIG. FIG. 7 shows a schematic representation of a malignant cell 20 with an HLA group 24 and an immunocompetent cell 30 with a receptor 32. Furthermore, FIG. 7
  • an antibody according to the invention can block or mask a receptor.
  • the receptor type 32 is basically capable of ligating the embryonic HLA group 24 of the malignant cell 20 and exerting an inhibitory effect on the immunocompetent cell 30 based on the binding of the embryonic HLA group 24.
  • the receptor 32 of the immunocompetent cell 30 is masked by an antibody 34.
  • the antibody 34 is of the type that specifically binds to the receptor 32 as a ligand and thereby blocks or sequesters the receptor 32 so that the embryonic HLA group 24 can not bind to the receptor 32 or only with less effect, on the other hand none inhibitory effect on the associated immunocompetent cell.
  • GnRH gonadotropin releasing hormone
  • the malignant cell 20 could bind to the inhibitory receptor 32 of the immunocompetent cell 30 by means of the HLA group 24 and thus a
  • the inhibitory receptor 32 can be masked and the escape mechanism inhibited.
  • the immune response of immunocompetent cell 30 is not inhibited.
  • the antibody can be used to treat the malignancy involving each individually associated immune system.
  • the antibody used to mask the inhibitory receptor 32 can be incorporated into a library of humanized antibodies to immunocompetent cell inhibitory receptor types. This means that the diversity of the library depends on the number of different inhibitory receptor types. If the binding of another expression pattern, for example of HLA pseudogenes, to these types of receptors (whose antibodies are already part of the library) to be blocked or masked, so no extension of the library (eg by production of new, humanized antibodies) is necessary, but it may be for the provision of
  • Antibodies can be accessed on the existing library.

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Abstract

L'invention concerne un procédé de fourniture d'un médicament destiné au traitement d'une malignité, intégrant le système immunitaire respectivement associé individuellement ainsi qu'un anticorps fournis selon ledit procédé et son utilisation, la structure de communication individuelle entre la malignité et le système immunitaire étant établie au moyen de la détermination d'un profil d'expression génétique des groupes HLA embryonnaires et au moyen de la détermination d'un type de récepteur présent sur/dans des cellules immunocompétentes et des anticorps étant fournis d'un tel type que lesdits anticorps se lient spécifiquement en tant que ligands à au moins un type de récepteur déterminé et lesdits anticorps bloquent ou masquent ainsi le récepteur de telle sorte que la partie du profil d'expression génétique ne se lie pas ou ladite partie peut se lier seulement encore de manière à faible action, mais ladite partie elle-même n'inhibant pas la cellule immunocompétente associée.
PCT/EP2018/054339 2017-02-27 2018-02-22 Médicament destiné au traitement de malignité WO2018153956A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
EP18707335.8A EP3586132B1 (fr) 2017-02-27 2018-02-22 Médicament destiné au traitement de malignité
CA3054495A CA3054495A1 (fr) 2017-02-27 2018-02-22 Medicament destine au traitement de malignite
US16/488,523 US20190376968A1 (en) 2017-02-27 2018-02-22 Medicament for Malignant Tumor Treatment
SG11201907869VA SG11201907869VA (en) 2017-02-27 2018-02-22 Medicament for malignant tumor treatment
ES18707335T ES2951762T3 (es) 2017-02-27 2018-02-22 Medicamento para el tratamiento de neoplasias malignas
JP2019567781A JP2020510695A (ja) 2017-02-27 2018-02-22 悪性腫瘍の治療のための薬剤
IL26889719A IL268897A (en) 2017-02-27 2019-08-25 A drug to treat a malignant tumor
JP2022189482A JP2023027134A (ja) 2017-02-27 2022-11-28 悪性腫瘍の治療のための薬剤

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DE102017001875.8 2017-02-27
DE102017001875.8A DE102017001875A1 (de) 2017-02-27 2017-02-27 Medikament zur Malignombehandlung

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EP (1) EP3586132B1 (fr)
JP (2) JP2020510695A (fr)
CA (1) CA3054495A1 (fr)
DE (1) DE102017001875A1 (fr)
ES (1) ES2951762T3 (fr)
IL (1) IL268897A (fr)
SG (1) SG11201907869VA (fr)
WO (1) WO2018153956A1 (fr)

Citations (5)

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WO2006070286A2 (fr) * 2004-12-28 2006-07-06 Innate Pharma S.A. Anticorps monoclonaux contre le nkg2a
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US20190376968A1 (en) 2019-12-12
JP2020510695A (ja) 2020-04-09
ES2951762T3 (es) 2023-10-24
EP3586132A1 (fr) 2020-01-01
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